RAD51B

Overview

RAD51B (RAD51 Paralog B) encodes a member of the RAD51 family of proteins involved in homologous recombination repair (HRR). It forms the BCDX2 complex with RAD51C, RAD51D, and XRCC2 to facilitate strand invasion and resolution of DNA double-strand breaks. Germline and somatic alterations in RAD51B contribute to genomic instability and have been implicated in multiple cancer types. In the context of pediatric sarcomas, RAD51B alterations have been identified as relapse-specific events, suggesting a role in acquired genomic instability during tumor progression.

Alterations observed in the corpus

  • Somatic alteration in fusion-negative rhabdomyosarcoma (FN-RMS): RAD51B was identified as part of a cluster of DNA repair gene alterations (alongside RAD21, RAD51C, ATR, ATM, FANCA, FANCC) found exclusively at relapse in FN-RMS patients with higher mutational counts, indicating acquisition during progression rather than at diagnosis. PMID:37730754
  • In mCRPC, RAD51B was among the broader DNA-repair/recombination pathway alterations contributing to the 22.7% aggregate in the SU2C–PCF 150-case cohort. PMID:26000489
  • Intron-5 partner in a MYBL1 truncation event (AC78) in adenoid cystic carcinoma PMID:26631609
  • Novel partner locus in 1/20 ACC tumors; downstream region contains smaller enhancers that are translocated to MYB, driving MYB overexpression PMID:26829750
  • Recurrent translocation partner of HMGA1/HMGA2 (14q24.1 breakpoints) in endometrial polyps (WGS, 23 polyps); intragenic and downstream breakpoints observed; not considered a classical driver in this context PMID:28445112
  • RAD51B shows recurrent focal deletions (n=10, 2%) at 14q24.1 in MIBC; a new finding not seen in the original 131-tumor cohort PMID:28988769

Cancer types (linked)

  • RMS: DNA repair gene alterations including RAD51B were detected exclusively at relapse in FN-RMS tumors displaying higher somatic mutational burden, consistent with a mutator phenotype emerging during clonal evolution. PMID:37730754

Co-occurrence and mutual exclusivity

  • RAD51B alterations co-occurred with other DNA repair gene defects (RAD21, RAD51C, ATR, ATM, FANCA, FANCC) specifically at relapse in FN-RMS, suggesting a pattern of concomitant HRD pathway disruption in genomically unstable tumors. PMID:37730754

Therapeutic relevance

  • No direct therapeutic targeting of RAD51B was reported in the corpus. However, HRD pathway deficiency (of which RAD51B loss is a component) is a recognized biomarker of sensitivity to PARP inhibitors and platinum-based therapies in other cancer contexts; this connection has not yet been established in RMS.

Open questions

  • Whether RAD51B alteration is a driver or passenger event at RMS relapse remains unclear; the study identified it as part of a broader HRD gene cluster but did not individually characterize functional consequences. PMID:37730754
  • The specific alteration class (missense, truncating, deletion) for RAD51B in the rhabdomyosarcoma cohort was not individually reported. PMID:37730754

Sources

  • PMID:37730754 — de Traux de Wardin H et al., “Sequential genomic analysis using a multisample/multiplatform approach to better define rhabdomyosarcoma progression and relapse,” npj Precision Oncology (2023).

This page was processed by crosslinker on 2026-05-14. - PMID:26000489

This page was processed by crosslinker on 2026-05-14. - PMID:26631609

This page was processed by crosslinker on 2026-05-14. - PMID:26829750

This page was processed by wiki-cli on 2026-05-14. - PMID:28445112

This page was processed by wiki-cli on 2026-05-14. - PMID:28988769

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